Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer

Abstract : We previously demonstrated that hormone therapy (HT) and radiation therapy (RT) induce tumor-specific autoantibody responses in human prostate cancer, and this grant investigates the clinical significance of these findings. In Aim 1, the findings that HT induces autoantibody and T cell responses against PABPN1 in the Shionogi tumor model and that these immune responses are associated with inferior outcomes have recently been submitted for publication. We have also shown that the combination of HT+RT in this model leads to delayed tumor recurrence of a distal untreated tumor. Work is underway to determine whether similar antibody and T cell responses are seen in these mice and whether they too are associated with poor outcomes. In the human setting, we have tested known prostate cancer tumor antigens by ELISPOT and begun cloning our serologically-defined tumor antigens in order to test these against PBMCs collected from prostate cancer patients showing treatment-induced autoantibody responses (Aim 2). We have also continued to assemble cohorts of prostate cancer patients with recurrent versus non-recurrent disease at 5 years post-treatment (Aim 3). In summary, this study is progressing on schedule and is revealing unexpected results that we believe may be highly relevant to prognosis and treatment of prostate cancer.